Human histocompatibility antigens have been shown to be present in a soluble form in serum. What part do they play in the general immune system and what is their relationship to human disease? Our research plan is aimed at trying to answer these questions. Specifically we propose: (1) to determine the structure of the serum HL-A antigen; (2) to measure the levels of HL-A in serum from healthy persons and disease patients; and (3) to investigate the potentialities of using serum HL-A to prolong graft survival. The methods we will use to isolate serum HL- A are ion exchange and affinity chromatography and preparative gel electrophoresis. The molecular structure would be determined by analyzing the native antigen, the reduced and papain-digested antigen by analytical SDS electrophoresis and ultracentrifugation. The levels of HL-A in the serum would be measured by inhibition of monospecific HL-A alloantisera against most of the HL-A antigens. Investigations into the potentialities of using serum HL-A antigens to prolong graft survival would be made by: (1) in vitro tests; (2) animal studies; and eventually clinical trials (a separate project). The in vitro tests would involve testing purified and semipurified samples of serum HL-A antigens and antigen-antibody complexes for blocking certain tests which mimic the immune response in vivo (e.g. MLC, CMI, CML, LDA). The animal would involve treating mice of one strain (A) with serum histocompatibility antigens from a donor strain (B) to prolong the survival of B strain grafts transplanted into A. The ultimate goal is to determine the chemical nature of HL-A, to establish its biologic role and to investigate its potential use in transplantation.